Is MAG p.Val343= (c.1029C>A) pathogenic?

MAG p.Val343= (c.1029C>A) is classified Likely benign in MAG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). Very rare (popmax 0.00339%, nfe); Associated with hereditary spastic paraplegia 75.

What condition is associated with MAG p.Val343= (c.1029C>A)?

MAG p.Val343= (c.1029C>A) is associated with hereditary spastic paraplegia 75 (ClinVar).

How common is MAG p.Val343= (c.1029C>A) in the general population?

MAG p.Val343= (c.1029C>A) is very rare (popmax 0.00339%, nfe) (gnomAD).

How is Autosomal recessive spastic paraplegia type 75 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MAG p.Val343=

c.1029C>A · rs750356821 · VCV3004846

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00339%, nfe)

Conditions

hereditary spastic paraplegia 75

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.038	GERP -1.4, phastCons 0.7
Overall
CADD	2.743	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00339% European (non-Finnish) · 40/1,180,056 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.0026% 42/1,614,080 alleles · very rare exomes 37/1,461,892 · genomes 5/152,188 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00339%	29,501
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,918

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MAG
Protein: p.Val343=
Coding: c.1029C>A
MANE Select: NM_002361
dbSNP: rs750356821
Type: single nucleotide variant
Location: chr19:35302506 (GRCh38)
Gene constraint: LOEUF 0.734 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.53
Residue 343: the ig-like c2-type 3 domain

Full MAG gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 75 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal recessive spastic paraplegia type 75 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

MAG p.Arg508Ter Pathogenic/Likely pathogenic ★★ same condition
MAG p.Ala307Val Uncertain significance ★★ ⚠ same condition
MAG p.Ala490Thr Uncertain significance ★★ ⚠ same condition
MAG p.Arg316Leu Uncertain significance ★★ ⚠ same condition
MAG p.Arg425Gln Uncertain significance ★★ ⚠ same condition
MAG p.Arg465His Uncertain significance ★★ ⚠ same condition
MAG p.Arg563Cys Uncertain significance ★★ ⚠ same condition
MAG p.Arg563His Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mag-p-val343 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown